Periodic Hormonogenesis—A New Phenomenon. Periodicity in Function of a Hormone-Producing Tumor in Man1

Abstract

Evidence for periodicity in adrenocortical production of cortisol and 17-ketosteroids was found during study of a patient with a very slow growing carcinoid-type malignant bronchial adenoma. The tumor caused adrenocortical hyperplasia and Cushing's syndrome as well as the superior vena caval syndrome. The large quantity of immunologically reactive ACTH found in the tumor as well as marked fluctuations in blood ACTH levels support the view that the periodicity in adrenal steroid production which was observed was due to periodicity in ACTH production by the tumor. The cyclical changes in cortisol production were of large magnitude and the peak-to-peak cycle length, as estimated during 2 cycles, was approximately 18 days. During the cycles, urinary 17-hydroxycorticosteroids (17-OHCS) varied from normal to as high as 150 mg/day. Cyclical variations in renal sodium excretion also occurred and were not related to the rate of 17-OHCS excretion or to aldosterone excretion. Aldosterone excretion rates were distinctly low in spite of marked and prolonged dietary sodium restriction. Administration of metyrapone at a time cortisol production was low or administration of large amounts of dexamethasone when cortisol production was greatly increased did not affect cortisol production; hence, the production of ACTH-like material by the tumor was autonomous of stimuli commonly used to test the pituitary-adrenal feedback mechanism. This is believed to be the first documentation of periodicity in function of a hormone-producing neoplasm in man, and the term “periodic hormonogenesis” has been chosen to describe this phenomenon. The findings indicate that hormone production rhythms may exist in tumors, and suggest the possibility that this phenomenon occurs in a variety of neoplasms. Also, the fact that completely normal cortisol production may occur on a cyclical basis in the “ectopic ACTH syndrome” has not been reported previously and deserves emphasis because of the fundamental implications of the findings as well as the diagnostic confusion which may occur.